It is now well-established that human immunodeficiency virus type-1 (HIV-1) infection causes a slow but progressive impairment of the immune system and that a relentless destruction of CD4+ T cells represents another hallmark of HIV-1 infection.
The first immune cells to establish contact with invading HIV-1 are the dendritic cells (DCs) and their involvement in the initial response to HIV-1 is well-established.
For the moment, among the various HIV-1 cell surface receptors expressed in DCs, only the C-type lectin receptor known as dendritic cell immunoreceptor or DCIR has been shown to play a key role in viral dissemination, initiation of infection (Lambert et al. Blood 112, 1299-1307 (2008)) and antiviral immunity (Klechevsky, E., et al., Blood 116, 1685-1697 (2010)). Recently, it has been demonstrated that DCIR allows HIV-1 to attach to DCs and is involved in both phases of the transfer of HIV-1 from DCs to CD4TL (Lambert et al., supra). United States patent publication No. US 2010-0061991 teaches methods and therapeutic agents to prevent and/or control HIV infection by impairing the interaction between DCIR and HIV. International PCT patent publication No. WO 2012/021964 teaches methods and compounds for inhibiting DCIR signalling in mammalian cells.
The discovery of new therapeutic targets and the development of different therapeutic approaches based on these targets are necessary in order to pursue the fight against HIV. Current anti-HIV drugs and those in development target primarily the virus itself causing a risk of selection of resistant virus variants. In addition, existing treatments increase the lifespan of patients but they also contribute to increased co-morbidity.
Therefore, there is a need for methods, compounds and pharmaceutical compositions useful in the prevention and/or treatment of virus infections in subjects, more particularly in humans infected with or susceptible of HIV-1 infection. There is also a need for screening methods for identifying inhibitors of HIV-1, including in silico and computer based methods using a three-dimensional model of DCIR.